Sthoeger Z M, Bentwich Z, Zinger H, Mozes E
Department of Chemical Immunology, Weizman Institute of Science, Rehovot, Israel.
J Rheumatol. 1994 Dec;21(12):2231-8.
To determine the effects of the estrogen antagonist, tamoxifen, on the development and the course of experimental murine systemic lupus erythematosus (SLE).
SLE was induced in naive BALB/c female mice by injection of the human monoclonal anti-DNA antibody bearing the 16/6 idiotype (Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with tamoxifen (200-800 micrograms/mouse twice a week) up to a period of 8 months. In several mouse groups tamoxifen treatment was started as late as one year following the immunization with the 16/6 Id when overt disease was already observed.
Tamoxifen treatment had no effect on the 16/6 Id induced autoantibody production. However, the 16/6 Id immunized and tamoxifen treated mice demonstrated normal numbers of white blood cells (WBC) and thrombocytes while the untreated groups had significant leukopenia and thrombocytopenia. Similarly, persistent proteinuria and immune complex deposits in the kidneys were observed in the 16/6 Id immunized mice whereas no such deposits were found in kidney sections of 16/6 Id immunized mice that were treated with tamoxifen. Delayed tamoxifen treatment (starting a year following the immunization) also demonstrated beneficial therapeutic effects.
These studies demonstrate therapeutic effects of tamoxifen on murine experimental SLE suggesting a possible role for this estrogen antagonist in the treatment of human SLE and related disorders.
确定雌激素拮抗剂他莫昔芬对实验性小鼠系统性红斑狼疮（SLE）的发展及病程的影响。
通过注射携带16/6独特型（Id）的人单克隆抗DNA抗体，在未经处理的BALB/c雌性小鼠中诱导SLE。免疫六周后，当检测到高水平自身抗体时，用他莫昔芬（200 - 800微克/只小鼠，每周两次）治疗小鼠，持续8个月。在几个小鼠组中，他莫昔芬治疗直到用16/6 Id免疫一年后才开始，此时已观察到明显的疾病。
他莫昔芬治疗对16/6 Id诱导的自身抗体产生没有影响。然而，用16/6 Id免疫并接受他莫昔芬治疗的小鼠白细胞（WBC）和血小板数量正常，而未治疗组有明显的白细胞减少和血小板减少。同样，在16/6 Id免疫的小鼠中观察到持续性蛋白尿和肾脏中的免疫复合物沉积，而在用他莫昔芬治疗的16/6 Id免疫小鼠的肾切片中未发现此类沉积。延迟他莫昔芬治疗（免疫一年后开始）也显示出有益的治疗效果。
这些研究证明了他莫昔芬对小鼠实验性SLE的治疗作用，表明这种雌激素拮抗剂在治疗人类SLE及相关疾病中可能发挥作用。
